Journal of Natural Products Vol. 5 7 , No. 6, pp. 849-85 1,June 1994
849
A NEW SESQUITERPENE/PHENOLFROM THE AUSTRALIAN MARINE BROWN ALGA PERITHALlA CAUDATA S.J. ROCHFORTand R.J. CAPON*
School of Chemistry, Unamszty of Melbourne, Parhille, Victmia 3052, Australia AESTRACT.-A chemical re-investigation of the Australian marine brown alga Pwztbalia uudata has resulted in the isolation of the known reverse isoprenylated aromatic [I] and the related chroman 121, along with the new sesquiterpene/phenol131. The structure of 131 was confirmed by spectroscopic analysis.
Natural products of mixed sesquiterpene and quinol biosynthesis are common to marine brown algae and sponges (1). Known examples include acyclic, monocyclic, and bicyclic analogues with varying degrees of oxygenation and/or substitution in thearomatic subunit. This report describes the isolation and identification of a new example of this structural class from an Australian marine brown alga. Extraction of a sample of Peritbalia caudata Womersley (Sporochnaceae)with EtOH-CH,Cl, (9:1), followed by partitioning of the CH,Cl,-solubles and normal-phase (silica) chromatography, resulted in the isolation of three prenylated aromatics. The major component was identified by spectroscopiccomparison as the known Pwitbalia caudata metabolite [lf(2). Likewise, one of the minor components was identified as the chroman {27, which had previously been described (2) via acid- or uv-catalyzed cyclization of 1. Our attempts to induce this cyclization through exposure of 1 to Si gel at room temperature in the presence of sunlight, 0, and common extraction solvents over prolonged periods, proved
1
2
unsuccessful. Despite this, given the potential for such a process to occur during extraction and purification, it is difficult to confirm that 2 is a natural product and not an artifact of the isolation procedure. The remaining metabolite 3 displayed 'H- and ',C-nmr resonances that were consistent with a farnesyl side-chain incorporating an all trans geometry (3), as well as a trisubstituted benzene and a carboxylic acid moiety. These features, together with a molecular formula of CZZH3,,03,required that 3 be a farnesylsubstituted hydroxybenzoic acid. The presence of the phenolic functionality was supported by a characteristic ir absorption (3360 cm-'). The hydroxybenzoic acid moiety was also supported by the appearance of a significant ion peak at mlz 151 in the mass spectrum, corresponding to benzylic cleavage (C1 ' 4 - 2 ' ) . Although the 'H-nmr spectrum (CDC1,) of 3 displayed two aromatic protons with coincident resonances, a 1,2,4-aromatic substitution pattern was apparent from the appearance of the isolated aromatic proton as an ortho-coupled doublet (J=8.8 Hz). This assignment was further confirmed by analysis of the 'H-nmr spectrum (C,D,) of 3, which clearly revealed ortho-, ortho-/meta-, and meta-coupled aromatic protons, respectively. Irradiation of the benzylic methylene associated with the farnesyl sidechain revealed an nOe (2.8%) to the meta-coupled aromatic proton, thus placing them on adjacent aromatic carbons. That the meta- and ortho-/meta-coupled aromatic protons were significantly
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3
deshielded with respect to the orthocoupled aromatic proton permitted the substitution pattern to be established as shown. Compound 3 is structurally related to the corresponding isoprene homologue 4 previously isolated from the sponge Zrcinia sp. (4). Marine sesquiterpenes incorporating a prenylated p hydroxybenzoic acid functionality, although uncommon, have been described from both brown algae (e.g., Dictyopteris undulata,zonaric acid E57 ( 5 ) ; and sponges (e.g., Siphonodictyon coralliphagum, siphonodictyoic acid E67) (6). To date
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compound 3 represents the only example of this structure class incorporating an acyclic farnesyl side-chain. EXPERIMENTAL GENERAL EXPERIMENTAL PROCEDURES.-&tails of procedures can be found in Butler and Capon (7).
PLANT MATERIAL-A sample of the alga Pm’tbaiia c a d t a (210 g dry wt, Melbourne University Herbarium N“ MELU-A035023) collected by hand (scuba) offshore from Flinden, Victoria, was packed in ice and transported to the laboratory, where it was transferred to a polythene sample bottle and steeped in EtOH-CH,CI, (9:l). EXTRACTION AND ISOLATION.-The decanted plant extract was then partitioned into CH,CI,solubles (9.10 g) and CH,CI,-insolubles (8.78 g), with the former extract being subjected to further fractionation by rapid Si gel filtration [lo%
stepwise gradient from petroleum ether (40-604 to EtOAc] to yield 1 (2.252 g, 1.072%) plus a mixed fraction. The latter material was resolved by reversed-phase hplc (2.0 mllmin 5% H,O/MeOH through a Phenomenex Ultracarb 5 k m ODs-20 250X 10 mm column) to yield 2 (40 mg, 0.019%) and 3 (45 mg, 0.021%).
4-Hydroxy-3-( 1 ‘-((2’E,6’E)-3’, 7‘, 11’trimetbyi-2’, 6’, 1 O’-dodecatrienyi))-benzoic acid {3].-A colorless oil. Ir Y max (film) 3360, 1680, 1600 cm-’; ‘H nmr (400 MHz, CDCI,) 6 1.59 (6H, s, CH,-7’ and l l ’ ) , 1.67 (3H, s, CH,-3’), 1.78 (3H,s,H,-12’),2.12(8H,m,H2-4’,-5’,-8’, and -9‘), 3.39 (2H, d, J=7.3 Hz, Hz-l’), 5.08 (2H, m, H-6’ and -lo’), 5.33 ( l H , ddd, J=7.1, 7.1,and 1.4Ht,H-2’), 6.83 (lH,dJ=8.8Hz, 5H), 7.88 (2H, m, H-2 and H-6); ’H nmr (400 MHz, C6Dd 6 1.52 (6H, s, CH,-7’ and -11’), 1.57 (3H, S, CH3-3’), 1.68 (3H, S, H3-12’), 2.10 (8H, m, Hz-4’, - 5 ’ , -8‘, and -9’), 3.24 (2H, d,J=7 Hz, H,-l’), 5.21 (2H,m,H-6’andH-10’), 5.31 ( l H , m, H-2’), 6.39 ( l H , d,J=8.4 Hz, H-5), 8.02 ( l H , dd,J=8.4and2.2Hz,H-6),8.15 (lH,d,J=2.8 Hz,H-2); I3Cnmr(100MHz,CDC13) 16.0’, 16.3’, 17.7’(CH3-3’, -7’, -1l‘), 25.7 (q, C-12’), 26Ab(t, C-9’), 26.7b (t, C-8’), 29.4b(t, C-5’), 30.9b(t, C4’), 39.7(t,C-l’), 115.1 (d,C-5), 121.0(d,C-2‘), 121.5‘(s,C-3), 123.6‘(s,C-6‘), 124.4(d, C-lo’), 127.0d (s, C-I), 130.4 (d, C-61, 131.3d (s, C-7’), 132.5 (d, C-2), 135.5d(s,C-3’), 139.0 (s,C-ll’), 159.4 (s, C 4 ) , 171.6 (s, C-7’) ppm, assignments may be interwith identical superscriptsd” changed; eims (70 eV) mlz 342 (2), 189 (lo), 161 (9), 151 (34), 135(18), 109(19),93(21),81(42), 69(100), 54(27);hreimsm/z 342.2193 (C22H3003 requires 342.2195), 151.0396 (C,H,O, requires 151.0395). Or
ACKNOWLEDGMENTS WeacknowledgeG. Kraft for identifying the algal specimen. This research was funded by the Australian Research Council. LITERATURE CITED 1.
2.
3.
R.J. Capon, in: “Studies in Natural Products Chemistry.”Ed. by Atta-ur-Rahman, Elsevier Press,Amsterdam (1994). A.J. Blackman, C. Dragar, and R.J. Wells, Aust. J. Chem., 32,2783 (1979). M. Bonny and R.J. Capon,J. Nat. Prod., 57, 539 (1994).
June 19947 4. 5.
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R~hf01-tand Capon: Metabolites of Peritbalia
G. Cimino, S . De Stefano, and L. Minale, Experjentia, 28, 1401 (1972). G. Cimino, S. De Stefano, W. Fenical, L. Minale, and J.J. Sims, EXperentia, 31, 1250 (197 5 ). B.W. Sullivan, D.J. Faulkner, G.K.
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Matsumoto, H. Cun-Heng, and J. ClardyJ Org. C h . ,51,4568 (1986). M.S. Butler and R.J. Capon,Aurt.]. Chern., 45, 1705 (1992).
R e c e i d I 4 December I993
